BRCA - SUNY Downstate Medical Center · mutation. mutation. Tll h i h h accounted for in people of Ashkenazi decent Mutations are Tells the patient whether 185d lAG 538i C d she has

BRCABRCAGainosuke Sugiyama, MDGainosuke Sugiyama, MD

SUNY Downstate Medical CenterSUNY Downstate Medical CenterDepartment of SurgeryDepartment of Surgeryp g yp g y

www.downstatesurgery.org

Case PresentationCase PresentationCase PresentationCase Presentation

Patient had noticed a breast lump on the right sidePatient had noticed a breast lump on the right sidexx xx y/o femaley/o female

Patient had noticed a breast lump on the right side Patient had noticed a breast lump on the right side which has been enlarging for the past six months.which has been enlarging for the past six months.Patient denied any skin color changes, abnormal Patient denied any skin color changes, abnormal y g ,y g ,discharges, or pain at the site. discharges, or pain at the site. Underwent core needle biopsy which revealed invasive Underwent core needle biopsy which revealed invasive p yp yductalductal carcinoma. carcinoma.

Elective Right Modified Mastectomy


Case presentationCase presentationCase presentationCase presentation

PMHx: DM, HTN, Asthma, CHF: ejection fraction 40%PMHx: DM, HTN, Asthma, CHF: ejection fraction 40%PSHx: Left MRM in 1992 for ductal carcinoma.PSHx: Left MRM in 1992 for ductal carcinoma.Allergy: NKDAAllergy: NKDA

Family History: NonFamily History: Non--contributorycontributoryFamily History: NonFamily History: Non contributorycontributorySocial: no history of heavy alcohol consumption, Social: no history of heavy alcohol consumption, smoking, nor usage of oral contraceptives. smoking, nor usage of oral contraceptives. s o g, o usage o o a co t acept ves.s o g, o usage o o a co t acept ves.First age of Menarche was 13. First age of Menarche was 13. Last Menstrual Period was at age 53Last Menstrual Period was at age 53Last Menstrual Period was at age 53. Last Menstrual Period was at age 53.



Physical Exam: WNLPhysical Exam: WNLPhysical Exam: WNLPhysical Exam: WNLGeneral: well appearing, not in any distressGeneral: well appearing, not in any distressB EB EBreast Exam: Breast Exam:

Left chest + well healed mastectomy scarLeft chest + well healed mastectomy scarRight breast: + 3cm palpable hard mass at 11 o’clockRight breast: + 3cm palpable hard mass at 11 o’clockno nipple retraction, ulcerations, or abnormal no nipple retraction, ulcerations, or abnormal discharges presentdischarges present



Patient was taken to OR for Patient was taken to OR for Rt Modified Radical Rt Modified Radical MastectomyMastectomyPatient had uneventfulPatient had uneventfulPatient had uneventful Patient had uneventful recovery from the surgery recovery from the surgery and was discharged home on and was discharged home on POD #1 with Jackson PrattPOD #1 with Jackson PrattPOD #1 with Jackson Pratt POD #1 with Jackson Pratt drains. drains. Final Pathology: Invasive Final Pathology: Invasive Ductal Carcinoma AxillaryDuctal Carcinoma AxillaryDuctal Carcinoma. Axillary Ductal Carcinoma. Axillary Node Negative for Node Negative for Metastases. Metastases.


Familial Breast Cancer: Familial Breast Cancer: Contribution of BRCA geneContribution of BRCA gene


StatisticsStatisticsStatisticsStatistics

Breast cancer is the second Breast cancer is the second leading cause of death after leading cause of death after lung cancer in women. lung cancer in women. An estimated 180,510 newAn estimated 180,510 newAn estimated 180,510 new An estimated 180,510 new breast cancer cases will be breast cancer cases will be diagnosed in 2007diagnosed in 200740 910 deaths from breast40 910 deaths from breast40,910 deaths from breast 40,910 deaths from breast cancer will occur in that same cancer will occur in that same year. year.

American Cancer Society: Cancer Facts and Figures 2007. Altanta, GA: American Cancer Society.


Risk FactorsRisk FactorsRisk FactorsRisk Factors

Age: Cumulative risk of breast cancer increases with age; Age: Cumulative risk of breast cancer increases with age; g g ;g g ;most cases occur after age 50.most cases occur after age 50.(1)(1)

Reproductive and Menstrual history: Breast Cancer riskReproductive and Menstrual history: Breast Cancer riskReproductive and Menstrual history: Breast Cancer risk Reproductive and Menstrual history: Breast Cancer risk increases with early menarche and late menopause, and increases with early menarche and late menopause, and reduced by early first full term pregnancy. reduced by early first full term pregnancy. (2,3)(2,3)

Oral contraceptive usage: increase in breast cancer risk Oral contraceptive usage: increase in breast cancer risk among long term users. among long term users. g gg g

1) Feurr EJ Wun LM Boring CC et al : The lifetime risk of developing breast cancer Journal of1) Feurr EJ, Wun LM Boring CC, et al.: The lifetime risk of developing breast cancer. Journal of National Cancer Institute 85 (11): 892-7.

2) Nard SA: Modifiers of risk of hereditary breast and ovarian cancer. Nat Rev Cancer 2 (2): 113-23, 2002

3) Antoniou AC, Shenton A, Maher ER, et al.: Parity and breast cancer risk among BRCA 1 and BRCA mutation Carriers. Breast Cancer Res 8 (6): R72, 2006.



Family History: Epidemiologic studies Family History: Epidemiologic studies have clearly established the role of have clearly established the role of family history as an important risk family history as an important risk factor for breast cancer. factor for breast cancer. After age and gender family history isAfter age and gender family history isAfter age and gender, family history is After age and gender, family history is the strongest known predictive risk the strongest known predictive risk factor for breast cancer. factor for breast cancer. Some of the hereditary risk factors for Some of the hereditary risk factors for yybreast cancer can be attributed to breast cancer can be attributed to known mutations in single cancer known mutations in single cancer susceptibility genes. susceptibility genes.

1) Feurr EJ, Wun LM Boring CC, et al.: The lifetime risk of developing breast cancer. Journal of National Cancer Institute 85 (11): 892-7.

2) N d SA M difi f i k f h dit b t d i N t R2) Nard SA: Modifiers of risk of hereditary breast and ovarian cancer. Nat Rev Cancer 2 (2): 113-23, 2002




Hereditary breast cancer is Hereditary breast cancer is characterized by early age at onset characterized by early age at onset (5~15 years earlier than in sporadic (5~15 years earlier than in sporadic cases)cases)BilateralBilateralBilateralBilateralVertical transmission through both Vertical transmission through both maternal and paternal linesmaternal and paternal linesFamilial associations with tumorsFamilial associations with tumorsFamilial associations with tumors Familial associations with tumors of other organs, particularly the of other organs, particularly the ovary and prostate gland. ovary and prostate gland.

1) Feurr EJ, Wun LM Boring CC, et al.: The lifetime risk of developing breast cancer. Journal of National Cancer Institute 85 (11): 892-7.

2) Nard SA: Modifiers of risk of hereditary breast and ovarian cancer Nat Rev2) Nard SA: Modifiers of risk of hereditary breast and ovarian cancer. Nat Rev Cancer 2 (2): 113-23, 2002



Robson, M, Offit, K: Management of an Inherited Predisposition to Breast Cancer. The New England Journal of Medicine (357): 154-62


BRCA 1BRCA 1BRCA 1BRCA 1Susceptibility gene for breast cancer.Susceptibility gene for breast cancer.Susceptibility gene for breast cancer. Susceptibility gene for breast cancer. It was mapped by genetic linkage to the long arm of It was mapped by genetic linkage to the long arm of chromosome 17. chromosome 17. Mutations in the BRCA 1 appears to be responsible for Mutations in the BRCA 1 appears to be responsible for disease in 45% of families with multiple cases of breast disease in 45% of families with multiple cases of breast ppcancers onlycancers onlyPresent in up to 90% of families with both breast and Present in up to 90% of families with both breast and ovarian cancer. ovarian cancer.

Hall JM Lee MK Newman B et al : Linkage of early onset familial breast cancer toHall JM, Lee MK, Newman B, et al.: Linkage of early onset familial breast cancer to chromosome 17q21. Science (4988): 1684-9, 1990


BRCA 2BRCA 2BRCA 2BRCA 2A second breast cancer susceptibility gene, located on A second breast cancer susceptibility gene, located on chromosome 13. chromosome 13. (1)(1)

This was found on linkage studies of 15 families with This was found on linkage studies of 15 families with lti l f b t th t t li k d tlti l f b t th t t li k d tmultiple cases of breast cancer that were not linked to multiple cases of breast cancer that were not linked to

BRCA 1. BRCA 1. (1)(1)

BRCA 2 mutations: thought to account for approximatelyBRCA 2 mutations: thought to account for approximatelyBRCA 2 mutations: thought to account for approximately BRCA 2 mutations: thought to account for approximately 35% of multiple breast cancer in families. 35% of multiple breast cancer in families. Associated with male breast cancer, ovarian cancer, Associated with male breast cancer, ovarian cancer, prostate cancer, and pancreatic cancer. prostate cancer, and pancreatic cancer. (2,3)(2,3)

1) Wooster R, Neuhausen SL Mangion J, et al.: Localization of a breast cancer susceptibility gene, BRCA 2, to chromosome 13q12-13. Science 265 (5181): 2088-90, 1994. q ( ) ,

2) Gayther Sa, Mangion J, Russell P, et al.: Variation of risks of breast and ovarian cancer associated wth different germline mutations of the BRCA 2 gene. Nat Genet 15 (1): 103-5.

3) Tonin P, Weber B, Offit K et al.: Frequency of recurrent BRCA 1 and BRCA 2 mutations in Ashkenazi Jewish breast cancer families. Nat Med 2 (11): 1179-83,1996.


Function of BRCA1/BRCA 2Function of BRCA1/BRCA 2Function of BRCA1/BRCA 2Function of BRCA1/BRCA 2

Th b h h d l d dTh b h h d l d dThey are both inherited as an autosomal dominant condition. They are both inherited as an autosomal dominant condition. Results in truncated protein. Results in truncated protein. From the studies looking at the carriers normal allele is deletedFrom the studies looking at the carriers normal allele is deletedFrom the studies looking at the carriers, normal allele is deleted. From the studies looking at the carriers, normal allele is deleted. This results in loss of all protein function. This results in loss of all protein function. This finding strongly suggests that the BRCA1/BRCA2 are This finding strongly suggests that the BRCA1/BRCA2 are tumor suppressor genes. tumor suppressor genes.

1) Smith SA, Easton DF Evans DG, et al.: Allele losses in the region 17q12-21 in familial breast and ovarian cancer involve the wild-type chromosome. Nat Genet 2 (2): 128-31,1992.

2) Collins N McManus R Wooster R et al : Consistent loss of the wild2) Collins N, McManus R, Wooster R, et al.: Consistent loss of the wild type allele in breast cancers from family linked o the BRCA 2 gene on chromosome 13q12-13. Oncogene 10 (8): 1673-5,1995.


Risk assessmentRisk assessmentRisk assessmentRisk assessment

There are several models available There are several models available to estimate a women’s risk of to estimate a women’s risk of having breast cancer. having breast cancer. Family history is the main Family history is the main determining factordetermining factordetermining factor. determining factor. Estimates of breast cancer risk for Estimates of breast cancer risk for carriers of BRCA 1 mutation by carriers of BRCA 1 mutation by the age of 80 years are 90%the age of 80 years are 90%g yg yFor BRCA 2 mutations carriers, For BRCA 2 mutations carriers, the risk is 40%.the risk is 40%.All of the risk vary according to the All of the risk vary according to the y gy gage of the patients. age of the patients.

Robson, Mark, Offit, Kenneth.: Management of an Inherited Predisposition to Breast Cancer. The New England Journal of Medicine (357): 154-62


Robson, M, Offit, K: Management of an Inherited Predisposition to Breast Cancer. The New England Journal of Medicine (357): 154-62


Genetic TestingGenetic TestingGenetic TestingGenetic Testing

There are several tests available to look forThere are several tests available to look forThere are several tests available to look for There are several tests available to look for BRCA 1/2 mutations. BRCA 1/2 mutations.

DNA sequencingDNA sequencingDNA sequencingDNA sequencingMultisite analysisMultisite analysisSingle Site anal sisSingle Site anal sisSingle Site analysisSingle Site analysis

Neuhausen, S. L. and Ostrander, E.A. (1997). Mutation testing of early-onset breast cancer genes BRCA1 and BRCA2. Genet Test 1(2): 75-83


Genetic TestingGenetic TestingGenetic TestingGenetic Testing

DNA sequencingDNA sequencingDNA sequencingDNA sequencingMost comprehensive testMost comprehensive testD ll h iD ll h iDetects all changes in a geneDetects all changes in a geneCan be ambigousCan be ambigousStill overlooks 5~10% of the mutationStill overlooks 5~10% of the mutation



Genetic TestingGenetic TestingGenetic Testing Genetic Testing

SingleSingle--site analysissite analysis Mutisite analysisMutisite analysisgg yyLooks for one mutation Looks for one mutation in family who already has in family who already has family member withfamily member with

yyLooks for three mutations Looks for three mutations that are most commonly that are most commonly accounted for in peopleaccounted for in peoplefamily member with family member with

known cancer causing known cancer causing mutation. mutation. T ll h i h hT ll h i h h

accounted for in people accounted for in people of Ashkenazi decentof Ashkenazi decentMutations are Mutations are 185d lAG 538i C d185d lAG 538i C dTells the patient whether Tells the patient whether

she has the mutation or she has the mutation or no mutation. no mutation.

185delAG,538insC, and 185delAG,538insC, and 617delT. 617delT. Limited to only these Limited to only these three genesthree genesMay still need to do May still need to do further testingfurther testinggg



Clinical ManagementClinical ManagementClinical ManagementClinical Management

Early detection and breast cancer surveillance is Early detection and breast cancer surveillance is a y detect o a d b east ca ce s ve a ce sa y detect o a d b east ca ce s ve a ce sthe most commonly employed method in the most commonly employed method in preventing breast cancer in patients who are at preventing breast cancer in patients who are at p v g b p wp v g b p wrisk. risk.


Clinical Management: Breast ExaminationClinical Management: Breast Examinationgg

Breast Examination:Breast Examination:MetaMeta--analyses of the studies analyses of the studies performed in women at performed in women at average risk showed no average risk showed no significant reduction in significant reduction in breast cancer mortality withbreast cancer mortality withbreast cancer mortality with breast cancer mortality with breast examination.(1)breast examination.(1)Showed increased rate of Showed increased rate of breast biopsies. (1)breast biopsies. (1)Clinician performed breast Clinician performed breast examination also did not examination also did not show significant detection show significant detection r t in p ti nt t r tr t in p ti nt t r trate in patients at average to rate in patients at average to high risks for breast cancer high risks for breast cancer in several large studies. in several large studies.

1) Hackshaw Ak, Paul EA. Breast self-examination and death from breast cancer: a meta-analysis. Br J Cancer 2003;88: 1047-53.

2) Robson, Mark, Offit, Kenneth.: Management of an Inherited Predisposition to Breast Cancer. The New England Journal of Medicine (357): 154-62


Clinical Management:MammographyClinical Management:MammographyClinical Management:MammographyClinical Management:Mammography

Mammography:Mammography:g p yg p yThere are no randomized, There are no randomized, controlled trials that examined controlled trials that examined the mammography as a the mammography as a

i l f hi h i ki l f hi h i kscreening tool for high risk screening tool for high risk patients.patients.

1) Brekelmans T, Seynaeve C, Bartels CC, et al. Effectiveness of breast cancer surveillance in BRCA1/2 genes mutation carriers and women with high familial su ve a ce C / ge es utat o ca e s a d wo e w t g a arisk. J Clin Oncol 2001; 19: 924-30.

2) Scheuer L, Kauff ND, Robson M, et al. Outcome of preventive surgery and screening for brast and ovarian cancer in BRCA mutation carriers. J Clin Oncol 2002; 20: 1260-8.


Clinical Management: MRIClinical Management: MRIClinical Management: MRIClinical Management: MRI

Several singleSeveral single--center andcenter andSeveral singleSeveral single center and center and multimulti--center studies have center studies have evaluated the efficacy of evaluated the efficacy of magnetic resonance magnetic resonance imaging(MRI) in women imaging(MRI) in women

i h h di i k fi h h di i k fwith a hereditary risk for with a hereditary risk for breast cancer. breast cancer.

Robson, Mark, Offit, Kenneth.: Management of an Inherited Predisposition to Breast Cancer. The New England Journal of Medicine (357): 154-62


Screening with magnetic resonance imaging andmammography of a UK population at high familial risk ofbreast cancer: a prospective multicentre cohort study

MARIBS (prospective multicenter cohort study)MARIBS (prospective multicenter cohort study)

breast cancer: a prospective multicentre cohort study(MARIBS)MARIBS study group*

(p p y)(p p y)Prospective multiProspective multi--center cohort study involving 649 women center cohort study involving 649 women ages 35ages 35--49 years49 yearsI l d ti t ith t f il hi t f b tI l d ti t ith t f il hi t f b tInvolved patients with strong family history of breast cancer Involved patients with strong family history of breast cancer or a high probability of a BRCA 1, BRCA 2, or TP 53. or a high probability of a BRCA 1, BRCA 2, or TP 53. Conclusion: MRI is more sensitive than mammography.Conclusion: MRI is more sensitive than mammography.Combination of Mammography and MRI would detect more Combination of Mammography and MRI would detect more cancers. cancers.

Leach MO, Boggis CR, Dixon AK, et al. Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: aand mammography of a UK population at high familial risk of breast cancer: a prospective mulicentre cohort study (MARIBS). Lancet 2005; 365: 1769-78.


Clinical Management:MRIClinical Management:MRIClinical Management:MRIClinical Management:MRI

Kriege et al (2004)Kriege et al (2004)Kriege et.al.(2004)Kriege et.al.(2004)Group of high risk patients were screened with MRI Group of high risk patients were screened with MRI and mammographyand mammographyand mammography.and mammography.Evaluated the efficacy of MRI and MammographyEvaluated the efficacy of MRI and Mammography1909 women screened w median follow up of 2 9 yrs1909 women screened w median follow up of 2 9 yrs1909 women screened w median follow up of 2.9 yrs1909 women screened w median follow up of 2.9 yrs358 women with germ line mutation carriers.358 women with germ line mutation carriers.

Kriege M, Breklemans CT, Boetes C, et al. Efficacy of MRI and mammography for breast cancer screening in women with aand mammography for breast cancer screening in women with a familial or genetic predispositions. New England Journal of Medicine 2004; 351: 427-37.


Concluded that in high risk patients, MRI appears to Concluded that in high risk patients, MRI appears to be more sensitive than mammography in detecting be more sensitive than mammography in detecting tumors.tumors.

Kriege M, Breklemans CT, Boetes C, et al. Efficacy of MRI and mammography for breast cancer screening in women with a familial or genetic predispositions. New England Journal of Medicine 2004; 351: 427-37.



Warner et al 2004Warner et al 2004Warner et al. 2004.Warner et al. 2004.Compared the sensitivity and specificity of 4 Compared the sensitivity and specificity of 4 methods of breast cancer surveillance in patientsmethods of breast cancer surveillance in patientsmethods of breast cancer surveillance in patients methods of breast cancer surveillance in patients with BRCA 1 or BRCA 2with BRCA 1 or BRCA 2

Sensitivity SpecificityMRI 77% 95.40%Mammography 36% 99.80%Ultrasound 33% 99.30%CBE 9.10% 99.30%

Warner E Plewes DB Hill KA et al Surveillance of BRCA 1 andWarner E, Plewes DB, Hill KA, et al. Surveillance of BRCA 1 and BRCA 2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA 2004; 292: 1317-25.



Conclusion:Conclusion:Conclusion: Conclusion: In BRCA1 and BRCA 2 mutation carriers, MRI is In BRCA1 and BRCA 2 mutation carriers, MRI is more sensitive for detecting breast cancers thanmore sensitive for detecting breast cancers thanmore sensitive for detecting breast cancers than more sensitive for detecting breast cancers than mammogram, ultrasound, or CBE alone. mammogram, ultrasound, or CBE alone. Further investigation is needed to study whether Further investigation is needed to study whether v s g s d d s dy wv s g s d d s dy wincluding MRI to surveilance for those patients who including MRI to surveilance for those patients who are high risk. are high risk.

Warner E Ple es DB Hill KA et al S r eillance of BRCA 1 andWarner E, Plewes DB, Hill KA, et al. Surveillance of BRCA 1 and BRCA 2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA 2004; 292: 1317-25.


Robson Mark Offit Kenneth : Management of an InheritedRobson, Mark, Offit, Kenneth.: Management of an Inherited Predisposition to Breast Cancer. The New England Journal of Medicine (357): 154-62.


Risk Reduction: ChemopreventionRisk Reduction: ChemopreventionNational Surgical Adjuvant Breast & Bowel National Surgical Adjuvant Breast & Bowel N g dj &N g dj &

Project (NSABPProject (NSABP--P1)P1)King et al 2001King et al 2001King et al. 2001King et al. 2001

Evaluated effect of Tamoxifen Evaluated effect of Tamoxifen on breast cancer among cancer on breast cancer among cancer free BRCA 1 and BRCA 2 free BRCA 1 and BRCA 2

i ii imutation carriersmutation carriersGenomic analysis was done on Genomic analysis was done on 288 patients who were 288 patients who were enrolled into the enrolled into the randomized,double blind randomized,double blind Breast Cancer Prevention Breast Cancer Prevention Trial.Trial.Outcome measures were Outcome measures were wwincidence of breast cancer in incidence of breast cancer in patients who received patients who received tamoxifen and placebotamoxifen and placebo

King MC, Wieand S, Hale K, et al. Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA 2001; 286: 2251-6




Risk Reduction: ChemopreventionRisk Reduction: ChemopreventionNational Surgical Adjuvant Breast & Bowel National Surgical Adjuvant Breast & Bowel N g dj &N g dj &

Project (NSABPProject (NSABP--P1)P1)

Conclusion: Tamoxifen reduced breast cancer Conclusion: Tamoxifen reduced breast cancer incidence among healthy BRCA 2 carriersincidence among healthy BRCA 2 carriersThis reduction was similar to reduction This reduction was similar to reduction incidence among ER positive breast cancer.incidence among ER positive breast cancer.No reduction was noted in BRCA 1 carriers.No reduction was noted in BRCA 1 carriers.No reduction was noted in BRCA 1 carriers. No reduction was noted in BRCA 1 carriers.



Risk Reduction: SurgeryRisk Reduction: SurgeryRisk Reduction: SurgeryRisk Reduction: Surgery

There is no randomized trials There is no randomized trials Reduction risk of breast Reduction risk of breast that evaluated the role of that evaluated the role of surgery in reducing breast surgery in reducing breast cancer in BRCA carrierscancer in BRCA carriers

cancer by approximately 50%cancer by approximately 50%

Reduction most likely relatedReduction most likely relatedSeveral retrospective and Several retrospective and prospective cohort studies prospective cohort studies have evaluated risk reducinghave evaluated risk reducing

Reduction most likely related Reduction most likely related to induction of premature to induction of premature menopause. menopause.

have evaluated risk reducing have evaluated risk reducing salpingosalpingo--oopherectomy oopherectomy (RRSO).(RRSO).Demonstrated reduction inDemonstrated reduction inDemonstrated reduction in Demonstrated reduction in risk of gynecologic cancer by risk of gynecologic cancer by 80~96%.80~96%.

Robson, Mark, Offit, Kenneth.: Management of an Inherited Predisposition to Breast Cancer. The New England Journal of Medicine (357): 154-62.



Rebbeck et al 2002Rebbeck et al 2002Rebbeck et al. 2002Rebbeck et al. 2002Examined the efficacy of bilateral prophylactic Examined the efficacy of bilateral prophylactic oopherectomy for reducing risk of coelomic andoopherectomy for reducing risk of coelomic andoopherectomy for reducing risk of coelomic and oopherectomy for reducing risk of coelomic and breast ca in BRCA 1 or 2 mutation carriersbreast ca in BRCA 1 or 2 mutation carriers551 women with either BRCA 1 or 2 mutations were 551 women with either BRCA 1 or 2 mutations were 55 w w s w55 w w s wexaminedexamined

Rebbeck TR, et al. Prophylactic oopherectomy in carriers f CA 1 CA 2 i h l dof BRCA 1 or BRCA 2 mutaitons. The New England

Journal of Medicine (346): 1616-1622.


Risk Reduction: SurgeryRisk Reduction: SurgeryRisk Reduction: SurgeryRisk Reduction: Surgery551 women with BRCA 1 or 2 mutations were 551 women with BRCA 1 or 2 mutations were identifiedidentifiedidentified.identified.259 underwent bilateral prophlactic oopherectomy259 underwent bilateral prophlactic oopherectomy292 matched control with no surgery292 matched control with no surgery292 matched control with no surgery292 matched control with no surgery6 pts received dx of ca @ the time of surgery6 pts received dx of ca @ the time of surgery2 pts received dx of serous peritoneal2 pts received dx of serous peritoneal2 pts received dx of serous peritoneal 2 pts received dx of serous peritoneal carcinomatosis after 3.8 and 8.8 yearscarcinomatosis after 3.8 and 8.8 years58 pts in control received dx of ovarian cancer after 58 pts in control received dx of ovarian cancer after

Rebbeck TR, et al. Prophylactic oopherectomy in carriers f CA 1 CA 2 i h l d

ppmean follow up of 8.8 yearsmean follow up of 8.8 years

of BRCA 1 or BRCA 2 mutaitons. The New England Journal of Medicine (346): 1616-1622.



241 out of 551 pts was dx with breast cancer241 out of 551 pts was dx with breast cancerpp99/241 patients had BPO99/241 patients had BPO142/241 was from the control142/241 was from the control142/241 was from the control142/241 was from the control21/99(21.2%) patients after BPO developed 21/99(21.2%) patients after BPO developed b tb tbreast cancerbreast cancer60/142(42.3%) patients from control developed 60/142(42.3%) patients from control developed

Rebbeck TR, et al. Prophylactic oopherectomy in carriers f CA 1 CA 2 i h l d

breast ca. breast ca.

of BRCA 1 or BRCA 2 mutaitons. The New England Journal of Medicine (346): 1616-1622.



CONCLUSION???CONCLUSION???••Bilateral prophylactic oopherectomy Bilateral prophylactic oopherectomy reduced the risk of coelomic epitheliumreduced the risk of coelomic epitheliumreduced the risk of coelomic epithelium reduced the risk of coelomic epithelium cancer by 96% in BRCA 1/2 carrierscancer by 96% in BRCA 1/2 carriers

••Risk of breast cancer reduced by 53%.Risk of breast cancer reduced by 53%.

Rebbeck TR, et al. Prophylactic oopherectomy in carriers of BRCA 1 or BRCA 2 mutaitons. The New England Journal of Medicine (346): 1616-1622.



Rebbeck, et al. 2004Rebbeck, et al. 2004Examined the efficacy of Examined the efficacy of bilateral prophylactic bilateral prophylactic mastectomy for breast cancer mastectomy for breast cancer in BRCA 1 and BRCA 2 in BRCA 1 and BRCA 2 mutation carriersmutation carriers483 women with BRCA 1/2 483 women with BRCA 1/2 mutations carriers underwent mutations carriers underwent bilateral prophylacticbilateral prophylacticbilateral prophylactic bilateral prophylactic mastectomymastectomyCompared to controls who had Compared to controls who had mutations but did not undergo mutations but did not undergo mastectomymastectomymastectomy. mastectomy.

Rebbeck TR, Friebel T, Lynch HT, et al. Bilateral Prophylactic mastectomy reduces breast cancer risk Rebbeck TR, Friebel T, Lynch HT, et al. Bilateral Prophylactic mastectomy reduces breast cancer risk in BRCA 1 and BRCA 2 mutations carriers: the PROSE Study Group. J Clin Oncol 2004;22: 1055in BRCA 1 and BRCA 2 mutations carriers: the PROSE Study Group. J Clin Oncol 2004;22: 1055--62.62.



They were matched to They were matched to cases on gene, center, and cases on gene, center, and year of birth. year of birth. Breast cancer was Breast cancer was wwdiagnosed in 2/105(1.9%) diagnosed in 2/105(1.9%) patients who underwent patients who underwent prophylactic mastectomy.prophylactic mastectomy.Breast cancer wasBreast cancer wasBreast cancer was Breast cancer was diagnosed in diagnosed in 184/378(48.7%) matched 184/378(48.7%) matched patients. patients. C l i Bil t lC l i Bil t lConclusion: Bilateral Conclusion: Bilateral prophylactic mastectomy prophylactic mastectomy reduces breast cancer risk reduces breast cancer risk in BRCA 1/2 carriers by in BRCA 1/2 carriers by 90%90%90%. 90%.

Rebbeck TR, Friebel T, Lynch HT, et al. Bilateral Prophylactic mastectomy reduces breast cancer risk in BRCA 1 and BRCA 2 mutations carriers: the PROSE Study Group. J Clin Oncol 2004;22: 1055-62.


Proposed AlgorithimProposed Algorithim

Rosenthal, TC, Stirling MP. Screening for Genetic Risk of Breast Cancer. American Rosenthal, TC, Stirling MP. Screening for Genetic Risk of Breast Cancer. American Family Physician. Jan. 1999Family Physician. Jan. 1999


SummarySummarySummarySummary

BRCA 1 and 2 are the most common hereditaryBRCA 1 and 2 are the most common hereditaryBRCA 1 and 2 are the most common hereditary BRCA 1 and 2 are the most common hereditary mutation causing breast cancermutation causing breast cancerEarly surveillance and detection is importantEarly surveillance and detection is importantEarly surveillance and detection is importantEarly surveillance and detection is importantUsage of Mammography and MRI is very useful Usage of Mammography and MRI is very useful

l f d i bl f d i btool for detecting breast cancertool for detecting breast cancerBilateral prophylactic oopherectomy and Bilateral prophylactic oopherectomy and mastectomy can reduce the risk of breast cancer mastectomy can reduce the risk of breast cancer and coelomic cancer. and coelomic cancer.


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BRCA - SUNY Downstate Medical Center · mutation. mutation. Tll h i h h accounted for in people of Ashkenazi decent Mutations are Tells the patient whether 185d lAG 538i C d she has